Mouse VL30 (retrotransposon) long terminal repeats (LTRs) are a potential source of tissue-specific transcriptional promoters that can be used to deliver and express therapeutic genes in humans. Such vectors are badly needed, because the current retroviral vectors appear to be effective only in hematopoietic cells in vivo. In phase I, a retro-vector system will be developed for rescuing LTR promoters, and for delivery and expression of foreign genes in a tissue-specific manner. Murine skeletal muscle, liver and dendritic cells will be used as the source for potentially tissue-specific promoters, which will be tested for reporter gene expression (green fluorescent protein) in homologous and heterologous human cells. A successful promoter-trapping vector will help to overcome the limited repertoire of cells that can presently be treated with retroviral vectors. Phase II work will use high-throughput combinatorial methods to generate highly specialized promoters for gene therapy.